IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate.
Ingenol mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with ingenol mebutate were not significantly different in C57BL/6 and Rag1...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4839727?pdf=render |
| _version_ | 1818118973068148736 |
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| author | Thuy T Le Kresten Skak Kate Schroder Wayne A Schroder Glen M Boyle Carly J Pierce Andreas Suhrbier |
| author_facet | Thuy T Le Kresten Skak Kate Schroder Wayne A Schroder Glen M Boyle Carly J Pierce Andreas Suhrbier |
| author_sort | Thuy T Le |
| collection | DOAJ |
| description | Ingenol mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with ingenol mebutate were not significantly different in C57BL/6 and Rag1-/- mice, suggesting B and T cells do not play a major role in the anti-cancer efficacy of ingenol mebutate. Relapse rates were, however, significantly increased in MyD88-/- mice and in C57BL/6 mice treated with the anti-IL-1 agent, anakinra. Ingenol mebutate treatment induces a pronounced infiltration of neutrophils, which have been shown to have anti-cancer activity in mice. Herein we provide evidence that IL-1 promotes neutrophil recruitment to the tumour, decreases apoptosis of infiltrating neutrophils and increases neutrophil tumour killing activity. These studies suggest IL-1, via its action on neutrophils, promotes the anti-cancer efficacy of ingenol mebutate, with ingenol mebutate treatment causing both IL-1β induction and IL-1α released from keratinocytes. |
| first_indexed | 2024-12-11T05:02:48Z |
| format | Article |
| id | doaj.art-24fac0083b674dda89eb20ed9aef36be |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T05:02:48Z |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-24fac0083b674dda89eb20ed9aef36be2022-12-22T01:20:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01114e015397510.1371/journal.pone.0153975IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate.Thuy T LeKresten SkakKate SchroderWayne A SchroderGlen M BoyleCarly J PierceAndreas SuhrbierIngenol mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with ingenol mebutate were not significantly different in C57BL/6 and Rag1-/- mice, suggesting B and T cells do not play a major role in the anti-cancer efficacy of ingenol mebutate. Relapse rates were, however, significantly increased in MyD88-/- mice and in C57BL/6 mice treated with the anti-IL-1 agent, anakinra. Ingenol mebutate treatment induces a pronounced infiltration of neutrophils, which have been shown to have anti-cancer activity in mice. Herein we provide evidence that IL-1 promotes neutrophil recruitment to the tumour, decreases apoptosis of infiltrating neutrophils and increases neutrophil tumour killing activity. These studies suggest IL-1, via its action on neutrophils, promotes the anti-cancer efficacy of ingenol mebutate, with ingenol mebutate treatment causing both IL-1β induction and IL-1α released from keratinocytes.http://europepmc.org/articles/PMC4839727?pdf=render |
| spellingShingle | Thuy T Le Kresten Skak Kate Schroder Wayne A Schroder Glen M Boyle Carly J Pierce Andreas Suhrbier IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. PLoS ONE |
| title | IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. |
| title_full | IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. |
| title_fullStr | IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. |
| title_full_unstemmed | IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. |
| title_short | IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate. |
| title_sort | il 1 contributes to the anti cancer efficacy of ingenol mebutate |
| url | http://europepmc.org/articles/PMC4839727?pdf=render |
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